The welfare and ethics of laboratory animals are the ethical principles and behavioral norms that need to be followed in conducting animal-based scientific research, breeding and managing laboratory animals, and supervising and regulating such activities. The level of protection of laboratory animal welfare and ethics is closely related to the development of science and technology, which has become a widely recognized international consensus. At present, Guangdong Province is accelerating the construction of a high-level science and technology innovation province and the Guangdong-Hong Kong-Macao Greater Bay Area International Science and Technology Innovation Center. Guangdong Province should rely on its advanced governance capacity in the field of laboratory animal science and technology ethics to promote the high-quality development of its laboratory animal science and technology sector. Based on the management laws, regulations, and institutional mechanisms of laboratory animals in China, this paper explores the optimization of the laboratory animal science and technology ethics governance system, which includes the institutional guarantees, responsibility systems, ethical review and supervision mechanisms, and education and outreach. Through methods such as literature research, questionnaire surveys, and interview investigations, an empirical study of the laboratory animal science and technology ethics governance system in Guangdong Province has been conducted. Analysis of literature and research results shows that Guangdong Province has basically established a laboratory animal management system, collaboration mechanism, supervision mechanism, and education and training system that meet the current requirements of the laboratory animal science and technology ethics governance system in China. However, there are still problems such as an incomplete laboratory animal science and technology ethics supervision mechanism, an underdeveloped operation mechanism of review institutions, insufficient attention paid by laboratory animal units to the ethical review of animal experiments, inconsistent ethical review standards, and a lack of professional ethical education and training for ethics review personnel. Therefore, optimization measures such as improving the laboratory animal science and technology ethics review system, strengthening supervision and inspection, further strengthening the accountability of responsible entities, formulating review norms, and enhancing hierarchical and classified education and training are proposed, to provide a theoretical basis for promoting the normalized and long-term governance of laboratory animal science and technology ethics in Guangdong Province.

ObjectiveTo explore the effect of Shenge Bushen Capsules （SBC） on sexual development in normal 3-week-old mice. MethodsThe experiment consisted of two parts. In the first part， mice were divided into four groups： The control group and the low， medium， and high-dose SBC groups （234.7， 469.4， 938.7 mg·kg^-1， respectively）. In the second part， mice were divided into four groups： Control group， Pseudostellariae Radix polysaccharide （PRP） group， total flavonoids group， and SBC group， all receiving a dose of 469.4 mg·kg^-1. After 7 days of administration， the vaginal opening of female mice and the descent of testes and scrotum in male mice， as well as the ovarian and testicular organ indices， were observed. After 4 weeks of administration， female and male mice were housed together for 2 days， and the pregnancy rate of females was monitored. After delivery， the pregnant female mice continued receiving the treatment for 4 weeks， and the sexual development of their offspring， including vaginal opening， testicular descent， and organ indices of ovaries and testes， was observed. Serum sex hormones were measured by enzyme-linked immunosorbent assay （ELISA）， and the expression of gonadotropin-releasing hormone （GnRH） and growth hormone （GH） proteins in the hypothalamus was assessed by Western blot. ResultsCompared with the control group， there was no significant effect on the vaginal opening of female mice or the descent of testes in male mice after 7 days of SBC administration. After 4 weeks of administration， the pregnancy rate in the low-dose group was significantly reduced （P<0.05）， but no significant effects were observed in the other groups. The three doses of SBC did not significantly affect the ovarian or testicular organ indices， and there was no significant upregulation in the expression of GnRH or GH in the hypothalamus. The primary component of SBC， Pseudostellariae Radix polysaccharide， significantly reduced the vaginal opening in female mice after 7 days of administration （P<0.05）. After 4 weeks， the serum estradiol levels of non-pregnant female mice were decreased （P<0.05）， but there was no significant effect on the expression of GnRH or GH proteins in the hypothalamus of either male or female mice. Additionally， there were no significant effects on precocious puberty indicators， such as vaginal opening and testicular descent， in the offspring mice. ConclusionSBC does not significantly promote precocious puberty in young mice， and it does not have any noticeable effects on the pregnancy rate of adult mice or the sexual development of their offspring.

Pheochromocytoma and intestinal ganglioneuromatosis are rare entities, associated with Multiple Endocrine Neoplasia Type 2B (MEN2B), but rarely associated with colonic pseudo-obstruction and ischemia. We report a 52-year-old patient who presented with colonic perforation and was later found to have all 3 pathologies concurrently. An exploratory laparotomy revealed toxic megacolon with rectosigmoid perforation requiring a total abdominal colectomy. Diffuse intestinal ganglioneuromatosis with no malignancy was reported by histopathology. Perioperative challenges included severe acidosis (pH 6.9) and supraventricular tachycardia requiring electrical and chemical cardioversion. Despite this, the patient was successfully managed with minimal vasopressor support (likely due to endogenous catecholamine release from his pheochromocytoma). This case of gastrointestinal emergency underlines the need for early recognition of comorbidities associated with MEN2B, and the importance of multidisciplinary care. This is the first case report describing bowel perforation in the context of MEN2B, pheochromocytoma, and intestinal ganglioneuromatosis.

Background: Patients who report to be difficult to anesthetize for dental procedures are commonly encountered.Determining their frequency and shared characteristics could improve understanding of pain management failures. Methods: Categorical and continuous variables of 24 demographic, medical history, and dental history variables were compared in a deidentified cross-sectional study using electronic health records (EHR) of patients at the University of Iowa College of Dentistry. Individuals who self-reported to be difficult to anesthetize in their dental health history form were compared to those who reported no complications with local anesthesia. Descriptive, univariate regression, and multivariable regression statistical analyses were completed on the demographic, medical history, and dental history EHR variables. Results: A total of 12,400 deidentified patient records met the inclusion criteria with a 11.4% (n = 1,411) prevalence of difficult to anesthetize self-reports. Eight categorical variables were found to have statistically significant (95% confidence interval [CI]) adjusted odds ratios (AOR) in the multivariable regression of difficult to anesthetize reporting patients: female gender (AOR = 1.61, 95% CI: 1.32-1.96, P < 0.001), dental fear (AOR = 3.60, 95% CI: 3.01-4.31, P < 0.001), mental health disorders (AOR = 1.21, 95% CI: 1.00-1.46, P < 0.045), problems with general anesthesia (AOR = 1.46, 95% CI: 1.11-1.89, P = 0.005), neurologicalerve disorders (AOR = 1.30, 95% CI: 1.05-1.60, P = 0.015), temporomandibular joint clicking/popping (AOR = 1.31, 95% CI: 1.08-1.60, P = 0.006), needle anxiety (AOR = 29.03, 95% CI: 23.80-35.52, P < 0.001), and history of root canal treatment (AOR 0.82, 95% CI: 0.68-0.99, P = 0.035). Conclusion A clinically relevant percentage of patients self-reported being difficult to anesthetize for dental procedures. The relationship between local anesthesia inadequacies and variables such as female gender, dental fear, mental health, and neurological disorders requires further investigation. The use of evidence-based local anesthesia approaches and communication practices is suggested to minimize pain experienced and subsequent fear of dental care.

Objective: In ovarian cancer (OvCa), tumor cell high glucocorticoid receptor (GR) has been associated with poor patient prognosis. In vitro, GR activation inhibits chemotherapyinduced OvCa cell death in association with transcriptional upregulation of genes encoding anti-apoptotic proteins. A recent randomized phase II study demonstrated improvement in progression-free survival (PFS) for heavily pre-treated OvCa patients randomized to receive therapy with a selective GR modulator (SGRM) plus chemotherapy compared to chemotherapy alone. We hypothesized that SGRM therapy would improve carboplatin response in OvCa patient-derived xenograft (PDX). Methods: Six high-grade serous (HGS) OvCa PDX models expressing GR mRNA (NR3C1) and protein were treated with chemotherapy +/− SGRM. Tumor size was measured longitudinally by peritoneal transcutaneous ultrasonography. Results: One of the 6 GR-positive PDX models showed a significant improvement in PFS with the addition of a SGRM. Interestingly, the single model with an improved PFS was least carboplatin sensitive. Possible explanations for the modest SGRM activity include the high carboplatin sensitivity of 5 of the PDX tumors and the potential that SGRMs activate the tumor invasive immune cells in patients (absent from immunocompromised mice). The level of tumor GR protein expression alone appears insufficient for predicting SGRM response. Conclusion The significant improvement in PFS shown in 1 of the 6 models after treatment with a SGRM plus chemotherapy underscores the need to determine predictive biomarkers for SGRM therapy in HGS OvCa and to better identify patient subgroups that are most likely to benefit from adding GR modulation to chemotherapy.

Background/Aims: Multiple rapid swallows (MRS) is a provocative test during high-resolution esophageal manometry (HRM) to evaluate contraction reserve (CR). This study aims to determine the prevalence of CR in patients with ineffective esophageal motility (IEM) and MRS performed in the upright position, and to assess the ideal number of MRS sequences. Methods: We enrolled adult patients diagnosed with IEM according to the Chicago classification version 4.0 who underwent HRM with 3 MRS sequences. Presence of CR was identified as either: the distal contraction integral (DCI) of the post-MRS sequence exceeding the mean DCI of single swallows (ratio > 1) or the mean DCI of the 3 post-MRS sequences surpassing the mean DCI of single swallows. The occurrence of CR was compared following 1, 2, and 3 MRS sequences. Results: When assessing CR in 57 patients referenced to mean single supine swallow DCI, the pooled prevalence of CR following 1, 2, and 3 MRS sequences was 23/57 (40.4%), 31/57 (54.4%), and 33/57 (57.9%), respectively. More patients had CR after 2 MRS sequences compared to 1 (P < 0.001), but there was no significant difference in CR between 2 and 3 MRS sequences (P = 0.160). More patients had CR after 2 (P = 0.013) and 3 MRS sequences (P = 0.034) when CR was referenced to single upright compared to single supine swallows. Conclusion Among patients with IEM, 58.0% had CR after 3 upright MRS sequences and 2 were adequate to assess CR.

Background/Aims: Buspirone shows promise in treating disorders of gut–brain interaction (DGBIs), particularly functional dyspepsia. However, findings have been mixed. Methods: We systematically searched for prospective studies testing buspirone for any upper gastrointestinal DGBI in 4 databases (Cochrane, PubMed, Scopus, and PsycInfo). The primary outcome was any validated measure of gastrointestinal symptoms. Anxiety, depression and adverse events were secondary outcomes. For randomized controlled trials (RCTs), we performed random-effects meta-analysis of the standardized mean difference (SMD) in post-treatment scores between buspirone and control groups. Risk of bias in RCTs was assessed using the Cochrane Common Mental Disorders Depression Anxiety and Neurosis Group (CCDAN) scale. Results: Ten studies (n = 283) met inclusion criteria, comprising 5 RCTs, 1 N-of-1 trial, 1 cohort, 1 case series, and 2 case reports. Tolerability of buspirone was good. In meta-analysis, buspirone produced a non-significant improvement in functional dyspepsia/gastroparesis symptoms compared to placebo (SMD = –0.14; 95% CI, –0.44 to 0.17; P = 0.39; I 2 = 0%; N studies = 3). Of individual symptoms, buspirone improved bloating severity more than placebo (SMD = –0.41; 95% CI, –0.77 to –0.04; P = 0.03; N studies = 2) but did not improve post-prandial fullness (P = 0.24, N studies = 2) or nausea (P = 0.75, N studies = 2). All RCTs included in the meta-analysis were good quality but most treated for only 4 weeks. Conclusions We found that buspirone did not improve functional dyspepsia symptoms more than placebo, though studies were small. Buspirone showed benefit for bloating severity, albeit based on few studies. Larger and longer trials of buspirone, targeting more defined groups such as patients with bloating, are warranted.

The scientific understanding of adipose tissue has advanced tremendously during the past decade. Once thought to be an inert fat storage organ, we now know that adipose tissue serves important functions in energy balance and endocrinology, as well as playing a central role in the development of metabolic diseases. Adipose tissue lipid storage and lipolysis are tightly controlled by hormones, such as insulin, in response to the body’s energy needs. Adipose insulin sensitivity can be measured in vivo in humans using isotopic fatty acid tracers and the insulin clamp technique. These data allow investigators to calculate the plasma insulin concentration that results in a 50% suppression of lipolysis. In obesity, insulin’s action on adipose tissue lipolysis is clearly impaired, resulting in excess free fatty acids in circulation, which can lead to metabolic dysfunction. However, the cause of this impairment is unclear. The chronic, low-grade adipose tissue inflammation seen in obesity was thought to be the cause of adipose tissue insulin resistance. In this review, we discuss the structure of adipose tissue, how normal and abnormal adipose tissue metabolism contributes to metabolic diseases, and how inflammation might or might not play a role in adipose tissue insulin resistance.

Background: and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups. Methods: ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model. Results: Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome. Conclusion Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.